DNA binding property, nuclease activity and cytotoxicity of Zn(II) complexes of terpyridine derivatives.
Two zinc(II) terpyridine complexes Zn(atpy)(2)(PF(6))(2) (1) (atpy = 4'-p-N9'-adeninylmethylphenyl-2,2':6,2''-terpyridine) and Zn(ttpy)(2)(PF(6))(2) (2) (ttpy = 4'-p-tolyl-2,2':6,2''-terpyridine) have been synthesized and characterized by elemental analysis, (1)H NMR and electrospray mass spectroscopy. The structure of complex 2 was also determined by X-ray crystallography, which revealed a ZnN(6) coordination in an octahedral geometry with two terpyridine acting as equatorial ligands. The circular dichroism data showed that complex 1 exhibited an ICD signal at around 300 nm and induced more evident disturbances on DNA base stacking than complex 2, reflecting the impact of the adenine moiety on DNA binding modes. Complex 1 exhibited higher cleavage activity to supercoiled pUC 19 DNA than complex 2 under aerobic conditions, suggesting a promotional effect of adenine moiety in DNA nuclease ability. Interestingly, both complexes demonstrated potent in vitro cytotoxicity against a series human tumor cell lines such as human cervix carcinoma cell line (HeLa), human liver carcinoma cell line (HepG2), human galactophore carcinoma cell line (MCF-7) and human prostate carcinoma cell line (pc-3). The cytotoxicity is averagely 10 times more active than the anticancer drug cisplatin.
Jiang
Qin
Q
Chemistry Department, Huaihai Institute of Technology, Lianyungang, 222005, People's Republic of China.
Zhu
Jianhui
J
Zhang
Yangmiao
Y
Xiao
Nan
N
Guo
Zijian
Z
D000225:Adenine / Q000737:chemistry; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D004278:DNA, Superhelical / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008968:Molecular Conformation; D011485:Protein Binding; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
D004278:DNA, Superhelical; D011725:Pyridines; D004247:DNA; D015032:Zinc; D000225:Adenine; C023666:pyridine